Back to Search
Start Over
Employing comparative QSAR techniques for the recognition of dibenzofuran and dibenzothiophene derivatives toward MMP-12 inhibition.
- Source :
-
Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2024 Sep; Vol. 42 (14), pp. 7304-7320. Date of Electronic Publication: 2023 Jul 27. - Publication Year :
- 2024
-
Abstract
- Among various matrix metalloproteinases (MMPs), MMP-12 is one of the potential targets for cancer and other diseases. However, none of the MMP-12 inhibitors has passed the clinical trials to date. Therefore, designing potential MMP-12 inhibitors as new drug molecules can provide effective therapeutic strategies for several diseases. In this study, a series of dibenzofuran and dibenzothiophene derivatives were subjected to different 2D and 3D-QSAR techniques to point out the crucial structural contributions highly influential toward the MMP-12 inhibitory activity. These techniques identified some structural attributes of these compounds that are responsible for influencing their MMP-12 inhibition. The carboxylic group may enhance proper binding with catalytic Zn <superscript>2+</superscript> ion at the MMP-12 active site. Again, the i -propyl sulfonamido carboxylic acid function contributed positively toward MMP-12 inhibition. Moreover, the dibenzofuran moiety conferred stable binding at the S1' pocket for higher MMP-12 inhibition. The steric and hydrophobic groups were found favourable near the furan ring substituted at the dibenzofuran moiety. Besides these ligand-based approaches, molecular docking and molecular dynamic (MD) simulation studies not only elucidated the importance of several aspects of these MMP-12 inhibitors while disclosing the significance of the finding of these QSAR studies and their influences toward MMP-12 inhibition. The MD simulation study also revealed stable and compact binding between such compounds at the MMP-12 active site. Therefore, the findings of these validated ligand-based and structure-based molecular modeling studies can aid the development of selective and potent lead molecules that can be used for the treatment of MMP-12-associated diseases.Communicated by Ramaswamy H. Sarma.
- Subjects :
- Catalytic Domain
Protein Binding
Binding Sites
Benzofurans chemistry
Benzofurans pharmacology
Ligands
Humans
Quantitative Structure-Activity Relationship
Thiophenes chemistry
Thiophenes pharmacology
Matrix Metalloproteinase 12 chemistry
Matrix Metalloproteinase 12 metabolism
Molecular Docking Simulation
Molecular Dynamics Simulation
Dibenzofurans chemistry
Matrix Metalloproteinase Inhibitors chemistry
Matrix Metalloproteinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-0254
- Volume :
- 42
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of biomolecular structure & dynamics
- Publication Type :
- Academic Journal
- Accession number :
- 37498149
- Full Text :
- https://doi.org/10.1080/07391102.2023.2239923